88899-55-2

Usage

Uses

Used in Pharmaceutical Industry:
Bafilomycin A1 is used as an antibacterial, antifungal, antineoplastic, and immunosuppressive agent due to its inhibitory effects on vacuolar-type ATPase. It prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes, which contributes to its therapeutic potential.
Used in Research Applications:
Bafilomycin A1 is used as a valuable tool for distinguishing among different types of ATPases in cell biology research. It helps in understanding the role of vacuolar-type H+-ATPase in various cellular processes.
Used in Neuroscience Research:
Bafilomycin A1 is used in neuroscience research to study the effects of pH regulation in brain cells and its role in lysosomal cholesterol trafficking in macrophages.
Used in Anticancer Research:
Bafilomycin A1 is used in cancer research to investigate its cytotoxic effects on various cell lines and its potential as an anticancer agent.
Used in Drug Delivery Systems:
Bafilomycin A1 can be incorporated into drug delivery systems to improve its bioavailability and therapeutic outcomes in targeted applications.
Used in Virology Research:
Bafilomycin A1 is used in virology research to study its effects on viral yield reduction in cell cultures infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its potential as an antiviral agent.

Biological Activity

Highly potent, selective inhibitor of vacuolar H + -ATPases (IC 50 = 500 pM as measured in chromaffin granule membranes). Selective over other ATP hydrolyzing enzymes such as F-ATPases, Ca 2+ -ATPases, Na + /K + -ATPases and plasma membrane H + -ATPases.

Biochem/physiol Actions

Bafilomycin A1 is a macrolide antibiotic. Bafilomycin A1 acts as a potent and selective inhibitor of vacuolar-type H+-ATPase.

References

1) Werner?et al.? (1984) Metabolic products of microorganisms. Bafilomycins, a new group of macrolide antibiotics. Production, isolation, chemical structure and biological activity; J. Antibiot.,?37?110 2) Drose and Altendorf? (1997)?Bafilomycins and concanamycins as inhibitors of V-ATPase and P-ATPase;?J. Exp. Biol.,?200?1 3) Yamamoto?et al. (1998)?Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells;?Cell Struct. Func.,?23?33

InChI:InChI=1/C35H58O9/c1-19(2)32-24(7)27(36)18-35(40,44-32)26(9)31(38)25(8)33-28(41-10)14-12-13-20(3)15-22(5)30(37)23(6)16-21(4)17-29(42-11)34(39)43-33/h12-14,16-17,19,22-28,30-33,36-38,40H,15,18H2,1-11H3/b14-12+,20-13+,21-16+,29-17-/t22-,23+,24-,25-,26-,27+,28-,30-,31+,32+,33+,35+/m0/s1

Upstream product

• 174657-23-9 C₅₀H₉₀O₉Si₂ 
• 243468-81-7 (3Z,5E,11E,13E)-(7R,8S,9S,15S,16R)-16-[(1R,2R,3S,6R,7S,8R)-2,8-Bis-(tert-butyl-dimethyl-silanyloxy)-6-hydroxy-1,3,7,9-tetramethyl-4-oxo-decyl]-3,15-dimethoxy-5,7,9,11-tetramethyl-8-triethylsilanyloxy-oxacyclohexadeca-3,5,11,13-tetraen-2-one 
• 381246-92-0 (2S,4S,5S)-7-methoxymethoxy-3,5-dimethylheptane-1,2,4-triol 
• 381247-21-8 (3S,4S)-4-Benzyloxymethoxy-5-(tert-butyl-diphenyl-silanyloxy)-3-methyl-pentan-1-ol 
• 139190-55-9 (3S,4S)-4-[(benzyloxy)methoxy]-5-(tert-butyldiphenylsilanyloxy)-3-methylpentanoic acid methyl ester 
• 381247-04-7 (3Z,5E,11E,13E)-(7R,8S,9S,15S,16R)-16-{(1S,2R,3S)-3-[2-((2R,3S,4R)-2,4-Dihydroxy-3,5-dimethyl-hexyl)-[1,3]dithian-2-yl]-2-hydroxy-1-methyl-butyl}-8-hydroxy-3,15-dimethoxy-5,7,9,11-tetramethyl-oxacyclohexadeca-3,5,11,13-tetraen-2-one 
• 154842-10-1 (R)-2-((4E,6E,12E,14Z)-(2R,3S,9S,10S,11R)-3,15-Dimethoxy-7,9,11,13-tetramethyl-16-oxo-10-trimethylsilanyloxy-oxacyclohexadeca-4,6,12,14-tetraen-2-yl)-propionaldehyde 
• 174420-18-9 (S)-4-[(1S,2R)-2-(tert-Butyl-dimethyl-silanyloxy)-1,3-dimethyl-butyl]-[1,3]dioxolan-2-one 
• 188938-27-4 (4S,5R)-2-(4-Methoxy-phenyl)-5-methyl-4-((S)-1-methyl-but-3-ynyl)-[1,3]dioxane 
• 174420-02-1 1-[(4R,5R)-2-(4-Methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-ethanone 
• 174420-04-3 (S)-2-[(4S,5R)-2-(4-Methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-propan-1-ol 
• 188938-26-3 (4R,5R)-4-Isopropenyl-2-(4-methoxy-phenyl)-5-methyl-[1,3]dioxane 
• 174420-01-0 (S)-1-[(4R,5R)-2-(4-Methoxy-phenyl)-5-methyl-[1,3]dioxan-4-yl]-ethanol 
• 174657-20-6 (2Z,4E,10E,12E)-(6R,7S,8S,14S,15R,16S)-7-(Diethyl-isopropyl-silanyloxy)-15-hydroxy-2,14-dimethoxy-17-[(4-methoxy-phenyl)-diphenyl-methoxy]-4,6,8,10,16-pentamethyl-heptadeca-2,4,10,12-tetraenoic acid 

Downstream Products

• 88899-58-5 monoacetyl-bafilomycin-A₁ 
• 88899-57-4 diacetyl-bafilomycin-A₁ 
• 88899-54-1 bafilomycin A2 
• 181464-10-8 C₄₂H₆₂O₁₀ 
• 88899-58-5 C₃₇H₆₀O₁₀ 

Relevant academic research and scientific papers

Diastereoselective Aldol Reactions of β-Silyloxy Ethyl Ketones. Application to the Total Synthesis of Bafilomycin A1

Studies directed toward the C17-C18 aldol bond construction in the macrolide antibiotic bafilomycin A1 are described.The effect of the β-substituent in the aldol reactions of α-unsubstituted enolates is documented for various model compounds.The stereoselectivity of this process is critically dependent on the C21 and C23 oxygen protecting groups.Application of this methodology to the synthesis of bafilomycin A1 is reported.

Total synthesis of bafilomycin A1

A convergent synthesis of bafilomycin A1 (see structure) is presented, and relies on the Zn(OTf)2-mediated diastereoselective addition of alkynes to aldehydes. The coupling of a complex enyne with a sensitive aldehyde in the key step

Total synthesis of (-)-bafilomycin A1

A highly stereoselective total synthesis of (-)-bafilomycin A1, the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and

Total synthesis of bafilomycin A1 relying on iterative 1,2-induction in acyclic precursors

The macrolide bafilomycin A1 was synthesized starting from D-valine and D-mannitol as chiral progenitors of propionate units. Acyclic subunits corresponding to different parts of the molecule were constructed based on an iterative 1,2-asymmetric induction protocol as a distinctive feature of the synthesis. The assembly of two segments encompassing the entire carbon framework of the macrolide was achieved by using a Stille coupling. The resulting seco-ester was further manipulated to provide crystalline bafilomycin A1 via a conventional carbodiimide-mediated Keck-type macrolactonization.

Retro-aldol cleavage of bafilomycin derivatives

The intermediates 3 and 4, useful in the preparation of new biologically active bafilomycin derivatives, were obtained via a thermal retro-aldol reaction in diphenyl ether. The starting materials 5 and 7 for the retro- aldol reaction were synthesized in a few steps from bafilomycin C1 (2) with or without a protective group at 7-OH.

Total synthesis of bafilomycin A1

The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A1 (1), the first specific potent inhibitor of vacuolar H+-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and β-hydroxyl hemiacetal side-chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A1. The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.

Total synthesis of bafilomycin A1. 2. The assemblage and completion of the synthesis

The total synthesis of the macrolide antibiotic, bafilomycin A1 (1), has been achieved by a convergent route involving aldol condensation between the 16-membered lactonic aldehyde 2 and the ethyl ketone 3, followed by desilylation.